RT Journal Article SR Electronic T1 Evidence for anticipation in autosomal dominant limb-girdle muscular dystrophy. JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 305 OP 308 DO 10.1136/jmg.35.4.305 VO 35 IS 4 A1 M C Speer A1 J M Gilchrist A1 J M Stajich A1 P C Gaskell A1 C A Westbrook A1 S K Horrigan A1 L Bartoloni A1 L H Yamaoka A1 W K Scott A1 M A Pericak-Vance YR 1998 UL http://jmg.bmj.com/content/35/4/305.abstract AB Anticipation, an increase in severity or decrease in age of onset (AO) inherent in the transmission of the disease gene from affected parent to affected child, has been increasingly described in human disease. To assess anticipation in a large kindred in which autosomal dominant limb-girdle muscular dystrophy (LGMD1A) is segregating, age of disease onset was collected from patient interviews of affected family members. A total of 25 parent-offspring pairs, in which the parents are three (3R), four (4R), or five (5R) generations removed from a common founding ancestor, were available for analysis. Life table analyses showed significant decreases in age at first reported symptoms in the offspring of the 3R (chi2=5.55, p=0.02) and 4R (chi2=7.81, p=0.005) parents. Pairwise analyses confirmed this decrease with a median decrease of 13 years in transmission to offspring from 3R parents and 18 years in transmission to offspring from 4R parents. The finding of anticipation in this pedigree suggests that the mutation in LGMD1A may be the result of the expansion of an unstable trinucleotide repeat.